chr2-73902768-G-A

Variant names:

• chr2-73902768-G-A
• rs1721244
• ENST00000409918.5:c.*40G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000409918.5(ACTG2):​c.*40G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 1,548,380 control chromosomes in the GnomAD database, including 261,461 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.56 (24220 hom., cov: 31)
  • Exomes 𝑓: 0.58 (237241 hom.)
• Consequence: ACTG2 ENST00000409918.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218
• Publications: 10 publications found

Genes affected

ACTG2 (HGNC:145): (actin gamma 2, smooth muscle) Actins are highly conserved proteins that are involved in various types of cell motility and in the maintenance of the cytoskeleton. Three types of actins, alpha, beta and gamma, have been identified in vertebrates. Alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins co-exist in most cell types as components of the cytoskeleton and as mediators of internal cell motility. This gene encodes actin gamma 2; a smooth muscle actin found in enteric tissues. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Based on similarity to peptide cleavage of related actins, the mature protein of this gene is formed by removal of two N-terminal peptides.[provided by RefSeq, Dec 2010]

ACTG2 Gene-Disease associations (from GenCC):

• visceral myopathy 1

  Inheritance: AR, AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• familial visceral myopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• megacystis-microcolon-intestinal hypoperistalsis syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACTG2	NM_001615.4	c.255+280G>A		intron_variant	Intron 3 of 8	ENST00000345517.8	NP_001606.1
ACTG2	NM_001199893.2	c.126+1331G>A		intron_variant	Intron 2 of 7		NP_001186822.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACTG2	ENST00000345517.8	c.255+280G>A		intron_variant	Intron 3 of 8	1	NM_001615.4	ENSP00000295137.3

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84765 AN: 151774 Hom.: 24202 Cov.: 31

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.653

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.714

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.562

GnomAD2 exomes AF: 0.596 AC: 89417 AN: 149968 AF XY: 0.585

Gnomad AFR exome AF: 0.447

Gnomad AMR exome AF: 0.766

Gnomad ASJ exome AF: 0.453

Gnomad EAS exome AF: 0.500

Gnomad FIN exome AF: 0.717

Gnomad NFE exome AF: 0.585

Gnomad OTH exome AF: 0.574

GnomAD4 exome AF: 0.580 AC: 809412 AN: 1396488 Hom.: 237241 Cov.: 41 AF XY: 0.577 AC XY: 397749 AN XY: 688842

African (AFR) AF: 0.448 AC: 14159 AN: 31590

American (AMR) AF: 0.748 AC: 26703 AN: 35678

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 11403 AN: 25156

East Asian (EAS) AF: 0.433 AC: 15470 AN: 35732

South Asian (SAS) AF: 0.499 AC: 39525 AN: 79162

European-Finnish (FIN) AF: 0.704 AC: 32980 AN: 46834

Middle Eastern (MID) AF: 0.447 AC: 2549 AN: 5700

European-Non Finnish (NFE) AF: 0.588 AC: 633994 AN: 1078520

Other (OTH) AF: 0.561 AC: 32629 AN: 58116

GnomAD4 genome AF: 0.558 AC: 84831 AN: 151892 Hom.: 24220 Cov.: 31 AF XY: 0.566 AC XY: 42044 AN XY: 74218

African (AFR) AF: 0.455 AC: 18846 AN: 41386

American (AMR) AF: 0.653 AC: 9962 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1511 AN: 3468

East Asian (EAS) AF: 0.486 AC: 2509 AN: 5164

South Asian (SAS) AF: 0.519 AC: 2497 AN: 4812

European-Finnish (FIN) AF: 0.714 AC: 7537 AN: 10558

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.591 AC: 40135 AN: 67934

Other (OTH) AF: 0.564 AC: 1189 AN: 2110

Alfa AF: 0.573 Hom.: 99516

Bravo AF: 0.552

Asia WGS AF: 0.552 AC: 1921 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	14
DANN	Benign	0.76
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1721244; hg19: chr2-74129895;